This project was developed and is directed by C.H. Paik, Ph.D. We have been developing chemical methods to radiolabel monoclonal antibodies and their fragments to use them as scintigraphic imaging agents to detect hematologic malignancies that express IL-2a receptors. For FY '98 we have extended our efforts to label genetically synthesized single chain, disulfide stabilized variable-region fragment (scdsFv) of antiTac monoclonal antibody with Tc-99m. The biodistribution of scdsFv was similar to that of dsFv, with its rapid tumor uptake whereas clearing rapidly from blood and all organs except kidneys. To improve its pharmacokinetic property with respect to its high renal uptake, we lowered the isoelectric point (pI 10) of scdsFv by acylation of its amino groups with succinic anhydride. This reaction neutralizes one positive charge on an amino group of scdsFv and at the same time adds one negative charge to dsFv. The succinic acid conjugated, Tc-99m-labeled scdsFv with a pI range of 4.4-6.4 showed the renal accumulation three to four times lower than that of the control Tc-99m-labeled scdsFv in tumor-bearing nude mice whereas its tumor uptake was not affected. Similarly, the whole-body retention of the succinic acid conjugate was much lower. The IL-2 receptor-positive ATAC4 tumor to non-tumor ratios increased steadily over time with ratios of 14.0, 13.6, 7.0, 22.8, 1.5, and 0.13 at 180 minutes for blood, the receptor-negative A431 tumor, liver, spleen, intestine, and kidney. This study suggests that the renal uptake of scdsFv involves charge interactions between positively charged scdsFv and negatively charged phopholipid bilayers of renal parenchymal cell membranes and that the lowering of the pI decreases the renal uptake. In conclusion, this study indicates that the high renal uptake of scdsFv can be optimized by chemical modifications without compromising tumor uptake.